Last updated: 07/17/2024 15:25:36
Dose Ranging Efficacy And Safety with Mepolizumab in severe asthmaDREAM
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A multicenter, randomized, double-blind, placebo-controlled, parallel group, dose ranging study to determine the effect of mepolizumab on exacerbation rates in subjects with severe uncontrolled refractory asthma
Trial description: The purpose of this study is to show whether mepolizumab given every 4 weeks intravenously (i.v.) can reduce the frequency of asthma exacerbations in subjects with severe asthma despite receiving high doses of standard asthma medications. The study will look at different doses of mepolizumab in comparison to a placebo.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Number of clinically significant exacerbations of asthma per year
Timeframe: From randomization (Week 0) to Week 52 or early withdrawal (EW)
Secondary outcomes:
Time to first clinically significant exacerbation requiring oral or systemic corticosteroid, hospitalization and/ or ED visit
Timeframe: From randomization (Week 0) to Week 52 or EW
Number of exacerbations requiring hospitalization (including intubation and admittance to an intensive care unit [ICU]) or ED visit per year
Timeframe: From randomization (Week 0) to Week 52 or EW
Time to first exacerbation requiring hospitalization or ED visit
Timeframe: From randomization (Week 0) to Week 52 or EW
Number of all recorded exacerbations per year
Timeframe: From randomization (Week 0) to Week 52 or EW
Time to first all recorded exacerbation
Timeframe: From randomization (Week 0) to Week 52 or EW
Mean change from Baseline in clinic pre-bronchodilator FEV1 over the 52-week treatment period
Timeframe: From Baseline up to Week 52 or EW
Mean change from Baseline in clinic post-bronchodilator FEV1 over the 52-week treatment period
Timeframe: From Baseline up to Week 52 or EW
Mean change from Baseline in asthma control questionnaire (ACQ) score over the 52-week treatment period
Timeframe: From Baseline up to Week 52 or EW
Interventions:
Biological/vaccine: Mepolizumab 750
Biological/vaccine: Mepolizumab 250
Biological/vaccine: Mepolizumab 75
Drug: Placebo saline
Enrollment:
621
Observational study model:
Not applicable
Primary completion date:
2012-23-03
Time perspective:
Not applicable
Clinical publications:
Pavord I, Korn S, Howarth P, Bleecker E, Buhl R, Keene O, Ortega H, Chanez P. Mepolizumab (anti-IL-5) reduces exacerbations in patients with refractory eosinophilic asthma. [Lancet]. 2012;380(August 18, 2012):
Katz LE, Gleich GJ, Hartley BF, Yancey SW, Ortega HG. Blood eosinophil count is a useful biomarker to identify patients with severe eosinophilic asthma. Ann Am Thorac Soc. 2014;11 (4):531-536.
Keene ON, Roger JH, Hartley BF, Kenward MG.Missing data sensitivity analysis for recurrent event data using controlled imputation.Pharma Stat.2014;13(4):258-64
Ortega H, Chupp G, Bardin P, Bourdin A, Garcia G, Hartley B, Yancey S, Humbert M. The role of mepolizumab in atopic or non-atopic severe asthma with persistent eosinophilia. Eur Respir J. 2014;44(1):239-41.
Ortega H, Li H, Suruki R, Albers F, Gordon D, Yancey S.Cluster analysis and characterization of response to mepolizumab: a step closer to personalized medicine for patients with severe asthma.Ann Am Thorac Soc.2014;11(7):1101-7
Pavord I, Korn S, Howarth P, Bleecker E, Buhl R, Keene O, Ortega H, Chanez P. Mepolizumab (anti-IL-5) reduces exacerbations in patients with refractory eosinophilic asthma. Lancet. 2012;380(August 18, 2012)
Kim MK, Park HS, Park CS, Min SJ, Albers FC, Yancey SW, Mayer B, Kwon N.Efficacy and safety of mepolizumab in Korean patients with severe eosinophilic asthma from the DREAM and MENSA studies.Korean J Intern Med.2020;
DOI: 10.3904/kjim.2019.198
PMID: 32450626
Medical condition
Asthma
Product
mepolizumab
Collaborators
GSK
Study date(s)
November 2009 to March 2012
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
12 - 65 years
Accepts healthy volunteers
No
- Male or female
- Aged 12 to 65 years inclusive
- Current smokers or smoking history of >=10 pack years
- Clinically important lung condition other than asthma
Inclusion and exclusion criteria
Inclusion criteria:
- Male or female
- Aged 12 to 65 years inclusive
- Minimum weight 45kg
- Clinical features of severe refractory asthma
- Well documented requirement for high dose inhaled corticosteroids (ICS) [i.e. >= 880mcg/day fluticasone propionate or equivalent daily] for at least 12 months
- Using additional controller medication in addition to high dose ICS for at least 12 months
- Persistent airflow obstruction indicated by a pre-bronchodilator FEV1<80% predicted at visit 1 or 2 or peak flow diurnal variability of >20% on 3 or more days during the run-in
- Airway inflammation which is likely to be eosinophilic in nature demonstrated by either raised peripheral blood eosinophils (>=300/microL), sputum eosinophils (>=3%), exhaled nitric oxide (>=50ppb) or prompt deterioration of asthma control following a <=25% reduction in regular maintenance dose of inhaled or oral corticosteroids (OCS)
- History of 2 or more exacerbations requiring systemic corticosteroids in the previous 12 months
- Evidence of asthma documented by airway reversibility, airway hyperresponsiveness or airflow variability
- ECG assessment demonstrating QTc<450msec or QTc<480msec for patients with bundle branch block
- Liver function tests demonstrating ALT<2xUpper Limit of Normal (ULN), AST<2xULN, Alk Phos <=1.5xULN, bilirubin <=1.5xULN
- Female of non-child-bearing potential or child-bearing potential with a negative pregnancy test at screening and prepared to agree to an acceptable method of contraception
- Able to give written informed consent
- Able to read, comprehend and write at a sufficient level to complete study materials
Exclusion criteria:
- Current smokers or smoking history of >=10 pack years
- Clinically important lung condition other than asthma
- Diagnosis of malignancy or in the process of investigation
- Unstable liver disease
- Churg-Strauss syndrome
- Using methotrexate, troleandomycin, oral gold, cyclosporine, azathioprine or any experimental anti-inflammatory therapy within 3 months of screening
- Omalizumab (Xolair) or any other biological for the treatment of inflammatory disease within 6 months of Visit 1
- Regular use of oral or systemic corticosteroids for diseases other than asthma within 12 months or any intra-articular, short-acting intramuscular corticosteroid within 1 month or intramuscular, long-acting depot corticosteroid within 3 months
- Allergy/intolerance to the excipients in the mepolizumab formulation
- Any investigational drug within 30 days or 5 terminal half-lives, whichever is longer
- Pregnant or breastfeeding or planning to become pregnant
- Clinically significant disease which is uncontrolled with standard treatment
- History of alcohol misuse or substance abuse
- Parasitic infestation within previous 6 months
- Known immunodeficiency
- Unable to follow instructions, use the electronic diary or peak flow meter
- Known evidence of lack of adherence to controller medications and/or follow physician's recommendations
- Previous participation in a study of mepolizumab and received study medication within 90 days
Trial location(s)
Location
GSK Investigational Site
Adelaide, South Australia, Australia, 5000
Status
Study Complete
Location
GSK Investigational Site
Buenos Aires, Buenos Aires, Argentina, 1425
Status
Study Complete
Location
GSK Investigational Site
Charleston, South Carolina, United States, 29406
Status
Study Complete
Location
GSK Investigational Site
Cheongju, Chungcheongbuk-do, South Korea, 361-711
Status
Study Complete
Location
GSK Investigational Site
Ciudad Autónoma de Buenos Aires, Argentina, C1426ABP
Status
Study Complete
Location
GSK Investigational Site
Denver, Colorado, United States, 80206
Status
Study Complete
Location
GSK Investigational Site
Frankfurt am Main, Hessen, Germany, 60596
Status
Study Complete
Location
GSK Investigational Site
Hershey, Pennsylvania, United States, 17033
Status
Study Complete
Location
GSK Investigational Site
Leicester, Leicestershire, United Kingdom, LE3 9QP
Status
Study Complete
Location
GSK Investigational Site
Lexington, Kentucky, United States, 40508
Status
Study Complete
Location
GSK Investigational Site
Long Beach, California, United States, 90808
Status
Study Complete
Location
GSK Investigational Site
Luebeck, Schleswig-Holstein, Germany, 23552
Status
Study Complete
Location
GSK Investigational Site
Madison, Wisconsin, United States, 53792
Status
Study Complete
Location
GSK Investigational Site
Magdeburg, Sachsen-Anhalt, Germany, 39112
Status
Study Complete
Location
GSK Investigational Site
Mainz, Rheinland-Pfalz, Germany, 55131
Status
Study Complete
Location
GSK Investigational Site
Mar del Plata, Buenos Aires, Argentina, B7600FZN
Status
Study Complete
Location
GSK Investigational Site
Nashville, Tennessee, United States, 37203
Status
Study Complete
Location
GSK Investigational Site
Nedlands, Western Australia, Australia, 6009
Status
Study Complete
Location
GSK Investigational Site
New Haven, Connecticut, United States, 06510
Status
Study Complete
Location
GSK Investigational Site
New Lambton, New South Wales, Australia, 2305
Status
Study Complete
Location
GSK Investigational Site
Oklahoma City, Oklahoma, United States, 73103
Status
Study Complete
Location
GSK Investigational Site
Pittsburg, Pennsylvania, United States, PA 15213
Status
Study Complete
Location
GSK Investigational Site
Puente Alto - Santiago, Región Metro De Santiago, Chile, 8207257
Status
Study Complete
Location
GSK Investigational Site
Riverside, California, United States, 92506
Status
Study Complete
Location
GSK Investigational Site
Ruedersdorf, Brandenburg, Germany, 15562
Status
Study Complete
Location
GSK Investigational Site
St. Louis, Missouri, United States, 63110
Status
Study Complete
Location
GSK Investigational Site
Suwon, Kyonggi-do, South Korea, 443-721
Status
Study Complete
Location
GSK Investigational Site
Valparaiso, Valparaíso, Chile, 2341131
Status
Study Complete
Location
GSK Investigational Site
Vancouver, British Columbia, Canada, V5Z 1M9
Status
Study Complete
Location
GSK Investigational Site
Winston-Salem, North Carolina, United States, 27103
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2012-23-03
Actual study completion date
2012-23-03
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Participate in clinical trial
Additional information
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
Click hereAccess to clinical trial data by researchers
Visit website